Mass spectrometry has benefited from numerous advances in ionization techniques over the past two decades. Among these ionization techniques, some are designed to operate on analytes presented in, or converted into gaseous form, such as atmospheric chemical ionization (APCI) and atmospheric pressure photoionization (APPI), others on analytes presented in liquid form, such as electrospray ionization (ESI), and still others on analytes presented in solid form, such as matrix-assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI). The latter techniques may be referred to as surface ionization techniques, since they involve desorption of analytes from a surface, followed by ionization of the analytes by various charge transfer processes.
Currently, MALDI (including AP-MALDI) is the most widely used surface ionization technique. In MALDI, analyte samples are diluted in a matrix material, deposited onto a surface, and then dried, whereby the analyte sample and matrix are co-crystallized. A pulsed laser beam, usually of ultraviolet (UV) frequency, is then focused onto the sample. The energy of the laser pulse is absorbed largely by the matrix, which desorbs (evaporates) from the surface, carrying with it analyte molecules. A portion of the desorbed matrix material is also ionized by absorption of laser radiation, and a portion of the desorbed analyte molecules is, in turn, ionized by a process of charge transfer from the matrix ions.
While MALDI has proven effective in many applications, the cost of the pulsed UV laser and its less-than-unlimited durability and reliability can be significant drawbacks. Furthermore, when analytes are prepared with matrix material, ions generated from the matrix create background noise at low mass levels. Additionally, co-crystallization of the matrix and analyte tends to be non-uniform, so that crystals are not uniformly distributed throughout the sample of interest. This non-uniformity necessitates rastering of the laser across the sample in small incremental steps, generally increasing the cost and complexity of the MALDI apparatus. These disadvantages have prompted the development of alternative surface ionization techniques that do not rely on the use of a laser or matrix material to generate analyte ions from a surface.
One surface ionization technique that does not rely on either a pulse laser or matrix-based sample preparation is desorption electrospray ionization (DESI). In this technique, an electrospray process is employed to generate a stream of ions that is directed at a low angle onto a sample-bearing surface. The stream of ions that is output collides with the surface, imparting sufficient energy to desorb and ionize analytes in the sample. While the DESI technique does not suffer from the above-mentioned drawbacks of the MALDI technique, it does require high voltages to generate ions through the electrospray process. Maintaining such high voltages (or high potential differences, depending on the configuration) also increases costs and instrumental complexity.